Dihydrolipoic acid inhibits tetrachlorohydroquinone-induced tumor promotion through prevention of oxidative damage.
alpha-Lipoic acid (LA) has been intensely investigated as a therapeutic agent for several diseases, including hepatic disorder and diabetic polyneuropathy. However, the effects of LA or its reduced form, dihydrolipoic acid (DHLA), on cancer chemoprevention has seldom been studied. Tetrachlorohydroquinone (TCHQ) is a toxic metabolite of pentachlorophenol (PCP) that was proven to be a tumor promoter in our previous study. We recently reported that DHLA can inhibit DMBA/TPA-induced skin tumor formation through its anti-inflammatory and anti-oxidizing functions. In the present study, we further examined the effects of DHLA on DMBA/TCHQ-induced skin tumor formation and the possible mechanisms. We found that DHLA significantly inhibited tumor incidence and tumor multiplicity in DMBA/TCHQ-induced skin tumor formation. Administration of DHLA prevented ROS generation, cytotoxicity, genotoxicity and apoptotic cell death in cells treated with TCHQ. In addition, activation of JNK and p38 MAPK may be involved in TCHQ-mediated apoptosis. Nonetheless, the detailed mechanisms of DHLA in attenuating TCHQ-induced skin tumor promotion are still unclear and need to be further investigated. We conclude that DHLA may be a useful protective agent against TCHQ-induced toxicity in epithelial cells, and for reversing TCHQ-induced damage in mouse skin.
Wang
Ying-Jan
YJ
Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan. yjwang@mail.ncku.edu.tw
Yang
Ming-Chen
MC
Pan
Ming-Hsiung
MH
D000818:Animals; D016588:Anticarcinogenic Agents; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004822:Epididymis / Q000473:pathology; D005434:Flow Cytometry; D006873:Hydroquinones / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D041681:NIH 3T3 Cells; D018384:Oxidative Stress / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000473:pathology / Q000517:prevention & control; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002273:Carcinogens; D006873:Hydroquinones; D018809:Proliferating Cell Nuclear Antigen; D017382:Reactive Oxygen Species; D008063:Thioctic Acid; C015144:dihydrolipoic acid; C044578:2,3,5,6-tetrachlorohydroquinone; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases